Risk Factors for Gallstones and Cholecystectomy: A Large-Scale Population-Based Prospective Cohort Study in Japan

Dig Dis. 2022;40(3):385-393. doi: 10.1159/000517270. Epub 2021 May 21.


Introduction: Studies investigating the risk of gallstones in the Japanese population are sparse. To our knowledge, this is the first prospective cohort study assessing risk factors of gallstones in Japan.

Methods: A nationwide population-based prospective cohort of 112,109 men and women, aged 40-69 years, self-completed questionnaires at baseline regarding exposures to potential risk factors, between 1990 and 1994. The occurrence of gallstones and cholecystectomy for gallstones were ascertained from another questionnaire after 10 years. Odds ratios and the 95% confidence intervals were calculated using the multivariate logistic regression.

Results: During the 10-year follow-up, 3,092 (5.0%) participants developed gallstones and 729 (1.2%) participants required cholecystectomy. Increasing age, high body mass index, and diabetes mellitus were associated with the risk of gallstones in both sexes. In men, weight gain or loss of >5 kg over the follow-up period and stress were associated with risk of gallstones, whereas alcohol intake was inversely associated with the risk. In women, weight gain of >5 kg during the follow-up period, smoking, menopause, and lipid-lowering drugs were associated with risk of gallstones, whereas late onset of menarche was inversely associated with risk of gallstones. The risk of cholecystectomy broadly reflected the risk of gallstones for both sexes respectively.

Conclusion: Risk factors for both gallstones and cholecystectomy for gallstones are multifactorial and differ between men and women. Novel findings in this study include an inverse association between late onset of menarche and gallstones, and an association between self-reported stress in men and gallstones.

Keywords: Cholecystectomy; Epidemiology; Gallstone disease; Gallstones.

MeSH terms

  • Cholecystectomy / adverse effects
  • Cohort Studies
  • Female
  • Gallstones* / complications
  • Gallstones* / epidemiology
  • Gallstones* / surgery
  • Humans
  • Japan / epidemiology
  • Male
  • Prospective Studies
  • Risk Factors
  • Weight Gain